Orthogonal cascades

Orthogonal cascades have been used to date for the removal of by-products in order to shift equilibrium. An excellent example of an orthogonal cascade is based on using alanine as an amino donor for the co-transaminase-catalyzed synthesis of chiral amines [49]. 

A second enz3me, p5U uvate decarboxylase, converts the by-product of the first reaction (p5U uvate) and creates a new by-product (CO ), making the thermodynamics of the second reaction very favorable and driving the first reaction (which is otherwise thermodynamically xmfavorable). Alternative systems could use lactate dehydrogenase, but this would then require an additional parallel system to recycle NAD+. 

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Orthogonal cascade. The final scheme is where substrates are supplied, or products removed, in situ via an addihonal enzyme. Such schemes are referred to as orthogonal cascades (Figure 20.2d). Such cascades are also foimd in nature, for example, to enable thermodynamically unfavorable reactions to take place. 

For parallel, cyclic, and orthogonal cascades more complex systems can be devised using a modular approach. The modules could also contain recovery options (for products or by-products), using liquid-liquid extraction or resin adsorption operations as required [35]. Such a modular approach can not only provide optimal conditions for each part of the process but can also enable operation in a flexible way to allow for the different time constants of operations and phenomena. A requirement for implementation of such technology is to find suitable methods of immobilization and retention of tiie catalysts in the reactor modules [35-37]. 

MaUcoch M, Thibault RJ, Drockenmuller E, Messerschmidt M, Voit B, RusseU TP, Hawker CJ. Orthogonal approaches to the simultaneous and cascade functionaUzation of macromolecules using cUck chemistry. J Am Chem Soc 2005 127 14942-14949. 

Molecules such as proteins, sugars, and DNA are constructed by Nature in complex environments via simultaneous and/or cascade reactions. This chemoselectivity is today recognized by chemists as the Holy Grail for synthesis towards traly monodisperse macromolecules. The foundation of such accomplishments is based on an initial definition of orthogonal systems, established in 1977 by Barany and Merrifield, who noted that ... 

M = mixture of feed and solvent. rn = A stage in a cascade. Orthogonal projection of M. m — A stage in a cascade. 

Figure 12.5 Schematic illustration of (a) simultaneous parallel and (b) cascade reactions performed on multifunctional macromolecules using click techniques in one-pot procedure. Such reactions are possible because of orthogonality of many click techniques. (Adapted from Sumerlin and Vogt, 2010.)...

Despite the significant benefit of using only a single enzyme, most TA methods rely on alanine as amine donor, making the removal of the coproduct pyruvate a crucial step. Consequently, different orthogonal enzyme cascades to shift the equilibrium toward amine formation were developed (Scheme 4.4). In general, these cascades combine two or three enzymes in a biocatalytic network. Two-enzyme... 

Riza et al. fabricated a three-terminal device for optical beam forming [6]. Figure 5.4 shows the top view of a thin film resistor-biased LC cylindrical lens, with electrical biasing resistors on the left and right sides of the active area. A spherical or elliptical lens can be formed by the appropriate use of a cascade of two such LC cylindrical lenses with orthogonal lens axes. 

A one-pot synthesis of 1,3-diamines was described in 2009 by Cordova and coworkers [17]. An asymmetric cascade aza-Michael/Mannich reaction was developed using a combination of diphenylprolinol trimethylsilyl ether 5 and proline as catalysts (Scheme 12.13). The cascade was possible because of the complete difference in reactivity between chiral pyrrolidine 5 and proline in the separate reactions. The conjugate addition of a protected methoxyamine to hex-2-enal was coupled to a three-component Mannich reaction, giving direct access to orthogonally protected chiral diamine derivatives with excellent chemo and enantioselectivities (yield 60-62%, ee 98-99%). The use of l-Pto as a catalyst for the Mannich reaction afforded the 6yn-l,3-diamine 30 (dr > 19/1), while the use of the antipode D-proline gave the anti derivative 31 with similar levels of diastereoselectivity. 

Instead, the orthogonal multienzymatic reactions are always cascade processes by definition. However, this type of multienzymatic processes has been largely investigated in the past especially for the development of enzymecofactor regeneration systems. These studies not only allowed the wide exploitation of cofactor-dependent enzymes, such as NAD(P)H-dependent dehydrogenases, by making their reactions economically feasible but were also useful in identifying relevant process options for the development of effective multienzymatic reaction systems (3). 

Using these two groups of multienzymatic systems as a basis, tiiere have been several attempts to classify such cascade reaction schemes [19, 24]. Three basic cascade schemes can be distinguished, namely, (1) linear, (2) parallel and cyclic, and (3) orthogonal. The motivation for implementahon in each case is a little different ... 

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